This invention concerns novel stereoisomers of 3-amino-2,6-dimethyl-bicyclo[2.2.1]-heptane-1,3-dicarboxylic acid, as well as methods for their preparation, isolation and use.
The Journal of Medicinal Chemistry (1999) 42, 1027-1040 describes the synthesis and pharmacological activity of a series of 4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acids (ABHDA""s) as group 11 metabotropic glutamate (mGlu) receptor agonists. The (xe2x88x92)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (ABHDA-I) is reported as a mGlu2 agonist with an EC50 value of 2.69 nM while the (xe2x88x92)-2-thia-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (ABHDA-II) displayed an EC50 value of 3.91 nM at the mGlu2 site. 
The synthesis and the pharmacological profile of a series of amino-bicyclo[2.2.1]heptane dicarboxylic acids (ABHD""s) as rigid analogues of 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) is described in Bioorganic and Medicinal Chemistry (1998) 6, 195-208. 2-endo-aminobicyclo[2.2.1]heptane-2-exo-7-anti-dicarboxylic acid (ABHD-I) is reported as a competitive antagonist at the mGlu1a receptor with a Kb value of 300 xcexcM. 
Both compounds (ABHD-I and ABHD-II) are described as agonists at the type 2 mGlu receptors.
Tocris Cookson Inc., 16144 Westwoods Business Park, Ellisville, Mis., 63021 (www.tocris.com) offers lists two isomers of aminotricyclo[2.2.1.0(2,6)]heptane-dicarboxylic acid. 
WO 9947490 claims a series of compounds described by the formula below in which n is 0-6, X is CH2, CH2CH or O, Z is CHR2 or NR2 and R1 and R2 are hydrogen, alkyl, aryl or heteroaryl as metabotropic glutamate receptor ligands useful for the treatment of a variety of neurological and psychiatric disorders. 
U.S. Pat. No. 6,124,361 (Chenard) teaches substituted bicyclo[3.1.0]hexane compounds of the formula: 
wherein n is an integer from 0 to 6; Z is (C1-C4) alkylene, oxygen, sulfur, NH or N(C1-C6)alkyl; and R1 is H or optionally substituted aryl or heteroaryl; which are metabotropic glutamate receptor ligands useful in the treatment of a variety of neurological and psychiatric disorders.